The Museum of the Western Prairie tells the story of Southwest Oklahoma, from the distant past to the present day. The narrative begins with the Wichita Mountains, the low, granite peaks that formed almost 300 million years ago. At first the Wichitas towered above the landscape; later they were islands in an ancient sea. Today the modest hills that remain serve as a connection between every era of Southwest Oklahoma history.

During the last Ice Age, the climate of the region supported animals that would later become extinct, such as the mammoth and mastodon. Their remains have been found repeatedly throughout the area. Ancient forms of bison, the ancestors of what were later called "buffalo" in North America, have also been found. Archaeological evidence reveals that humans hunted these animals in Southwest Oklahoma at least 11,000 years ago.

By 7,000 years ago, Paleo-Indians were present in Southwest Oklahoma. These people were hunters and gatherers who wandered on foot. Six-thousand years later, permanent settlements were established in some areas and farming began. One of the cultures connected with the historical period after European contact developed at this time, that of the Wichita.

Between the late 1550s and early 1700s, horses brought to North America by Europeans dispersed across the Plains. As a result many native groups transformed dramatically, becoming part of what are known broadly as the "Plains Indians." Their highly mobile lifestyle, based upon hunting the herds of bison that migrated north and south across interior North America, is a cultural image that persists today.

The Civil War (1861-1865) heralded a period of tremendous change in the United States. Although Southwest Oklahoma played no significant role in the conflict, it was directly effected by the events that followed. In particular, Texas ranchers began herding longhorns overland to meet a southern branch of the Transcontinental Railroad. This route, the Western Trail, passed through Southwest Oklahoma. At its peak in 1881, approximately 300,000 cattle, 7,000 horses, and 1,000 men moved up the trail. Altogether, more than 7,000,000 cattle traveled the route during its operation.

The years following the war also marked a period of severe change for the Plains Indians. Expanding settlements on the Southern Plains led to removal and confinement in the Indian Territory. Texas, which had no reservations, claimed modern Southwest Oklahoma as its own "Greer County" until 1896, but the Comanche, Kiowa, and others continued to visit the area seasonally as they had for hundreds of years. The drama of their eventual confinement on nearby reservations in the Indian Territory, bordering Greer County, played out all across the western reaches of the Red River, including present-day western and southwestern Oklahoma, and in adjacent areas of Texas.

With the destruction of the buffalo herds, the removal of the Indians, an ever-expanding rail system, and the increasing pressure to settle unclaimed land, eyes soon turned toward Southwest Oklahoma. But the environment was forbidding. The area was remote, there were few trees and so very little lumber, and water was scarce. Even in the 1880s Southwest Oklahoma was a difficult frontier. But the people adapted, as can be seen in the half-dugout on the museum grounds. The area developed rapidly and by the early 1900s, Southwest Oklahoma had well-established communities.

Both municipal growth and agricultural development emphasized the need for a large, stable water supply. Early successes such as Fullerton Dam on Turkey Creek near Olustee, Oklahoma, were followed by projects on the North Fork of the Red River. The Bureau of Reclamation completed Lake Altus in 1947, which irrigates approximately 48,000 acres in Southwest Oklahoma.

Today the western range of the Wichita Mountains presides over a largely agricultural base in Southwest Oklahoma, although the economy depends heavily on the presence of Altus Air Force Base, activated in 1953. In recent decades business has begun to further diversify, with new industry and tourism adding to the development of the area.